Biochemical effects of estrogen on articular cartilage in ovariectomized sheep.

Cartilage is a sex-hormone-sensitive tissue but the role of estrogen in the pathogenesis of osteoarthritis (OA) remains controversial. In this study, intrinsic material properties and thickness of articular cartilage of the knee joint of ovariectomized (OVX) and estrogen-treated sheep were measured. Skeletally mature ewes (N = 36, same breed, same housing 4-5 years old) were divided into; sham treated (n = 9), OVX (N = 13), OVX plus one estradiol implant (OVXE; N = 10) and OVX plus two estradiol implants (OVX2E; N = 4). Twelve months following sham procedure or OVX, sheep were euthanized and articular cartilage from a total of 216 points in the left femorotibial (knee) joints was tested for aggregate modulus, Poisson's ratio, permeability, thickness and shear modulus (six sites per sheep). When all of the sites in each knee were grouped together, OVX had a significant effect on articular cartilage. The sham cartilage of all sites grouped together had a larger aggregate modulus (P = 0.001) and a larger shear modulus (P = 0.054) than the OVX tissue. No statistically significant differences were seen for permeability and thickness between OVX, sham, OVXE and OVX2E. Differences existed in biomechanical properties at the different sites that were tested. Overall, no one location tended to be lowest or highest for all variables. This biomechanical study suggests that OVX may have a detrimental effect on the intrinsic material properties of the articular cartilage of the knee, even though the cartilage of the OVX animals appeared normal. Treatment with estradiol implants ameliorated these deleterious effects and may have helped maintain the tissue's structural integrity. Our study supports epidemiological studies of OA in women after menopause. The protective effect of estrogen and it's therapeutic effect remain to be further defined. This model may allow the relationship of estrogen and estrogen antagonists to be studied in greater detail, and may be valuable for the study of the pathogenesis and therapies of OA of postmenopausal women, particularly in its early stages.

A mechanical evaluation of the resistance of various interfragmentary wire configurations to torsion.

Fourteen interfragmentary orthopedic wire configurations were tested in torsion using a transverse fracture polyvinylchloride pipe model. These models included single and double Kirschner pins with and without orthopedic wire added to the configuration. The orthopedic wire was applied in either an encircling, figure-of-eight (skewer pin), or cruciate pattern. Double Kirschner pins were applied in a mono- or biplanar fashion. An external fixator model was also tested. Stiffness, yield load, safe load, and energy of absorption were measured and calculated for each model. Orthopedic wire added to any configuration increased stiffness. All single pin configurations with orthopedic wire and the external fixator had the highest stiffness. Two Kirschner pins had a higher torsional yield load and safe load than single pin configurations with or without orthopedic wire. The external fixator model had the highest torsional yield load, safe load and energy of absorption of all configurations tested. However, the external fixator was only significantly different in safe load from the 900 biplanar configurations with wire and the cross pin configuration with encircling wire. The 900 biplanar configurations with wire and the cross pin configuration with encircling wire were equally as effective as the external fixator model in yield load and energy of absorption.

The use of dual-energy x-ray absorptiometry in animals.

The use of dual-energy absorptiometry (DXA) to measure bone mineral content (BMC) and bone mineral density (BMD) is widespread in humans and has been adapted to animals because of the need to examine bone and body composition in longitudinal studies. In this review, the indications and techniques for DXA in small-sized animals (rodents, cats, and rabbits) and large-sized animals (dogs, swine, nonhuman primates, sheep, and horses) are discussed. Now that software has been developed for measuring BMD in small laboratory animals, the most frequent use of DXA in animals is in rats. An ultrahigh-resolution mode of acquisition is used for their small bones but also is necessary for other small-sized animals such as rabbits and cats. In larger-sized animals such as dogs, pigs, and sheep, software used in humans has been adapted successfully to measure BMC/BMD and body composition. The human spine and left and right hip protocols are adapted easily to animals of this size, and the software for body composition has been adapted to dogs. Measurement of bone mass around metallic implants is possible in animals and most studies have involved dogs. To ensure precision of DXA in the noninvasive measurement of BMD in animals, attention to positioning and ability of the operator to define the same region of interest using clearly defined anatomical landmarks on the scan image cannot be overemphasized. This is one of the essential requirements for successful densitometry in animals.

Dual-energy X-ray absorptiometry in sheep: experiences with in vivo and ex vivo studies.

As different large animal models of osteopenia and osteoporosis are explored, the use of DXA to rapidly, non-invasively and accurately estimate BMD will become widespread. We used DXA in live sheep and cadaveric material and the areas of trabecular bone that are most accessible on a simple, repeatable basis in the sheep were the lumbar vertebrae (L4-L6/L5-L7), the CAL and the DR. We performed dual-energy X-ray absorptiometry (DXA) using an Hologic QDR 1000-W bone densitometer to measure bone mineral density (BMD) at various regions of interest in anesthetized sheep and cadaveric specimens of sheep. In vivo measurements of L4-L6/L5-L7, the calcaneus (CAL) and distal radius (DR) in 48 intact 3 to 5-year-old ewes (same breed) were performed. Correlations between the different bones were investigated. In an in vivo precision study, BMD of L3-L6/L7, CAL and DR was determined with one animal repositioned between 10 scans of each bone. In another study, ex-vivo BMD measurements of the proximal and distal femur, proximal tibia, and proximal humerus were performed on isolated bones of 45 ewes of similar age. Excised vertebrae were scanned on the Hologic QDR 1000-W and on a Lunar DPX (at another site) and the data were compared. Correlations of BMD between individual vertebrae in anesthetized sheep were excellent (r = 0.944- 0.843; P < 0.0001). Correlation between BMD of individual vertebrae and CAL was good (r = 0.677-0.630), while correlation between BMD of individual vertebrae and DR was also good (r = 0.551-0.507; P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response effects of estradiol implants on bone mineral density in ovariectomized ewes.

In a longitudinal in vivo study, we studied the effect of two different doses of 17 beta-estradiol (E2) administered in the form of a subcutaneous implant, on bone mineral density (BMD) of the lumbar vertebrae (L4, L5, L4-L6/L5-L7), the calcaneus (CAL) and the distal radius (DR) in ovariectomized (OVX) ewes. The BMD of various regions of the femur, tibia and humerus were studied at autopsy. Skeletally mature ewes (n = 45) were divided into four groups: sham operated (n = 12), OVX (n = 15), OVX plus one E2 implant (OVXE, n = 12) and OVX plus two E2 implants (OVX2E, n = 6). BMD of L4, L5, L4-L6/L5-L7, CAL and DR was determined at 0, 6 and 12 months using dual-energy X-ray absorptiometry. In-vivo precision of BMD for the last three lumbar vertebrae ranged from 1.4-4.3%, and 1.5% and 3.5% for CAL and DR respectively. In the in vivo study, there were no significant changes in the mean BMD in the sham group at any time point (each group served as its own control). In the OVX group, mean BMD was significantly lower at L5 and DR at 6 months and significantly lower at L4 at 12 months. In the OVXE group, the mean BMD was significantly higher at L5, CAL and DR at 12 months. In the OVX2E group, BMD was significantly higher at CAL but significantly lower at L4 at 12 months. None of the treatments produced significant changes of mean BMD of L4-L6/L5-L7 at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)